Of Flavonoidw actions, healty anti-inflammatory action is prominent. Recent studies have demonstrated that certain flavonoid derivatives Anc affect pathways of inflammasome heaoth and autophagy.
Healh flavonoids can also accelerate the resolution Flaovnoids of inflammation, haelth to avoiding chronic inflammatory stimuli, Flavonoids and joint health. All these Flavknoids actions with newly emerging activities render flavonoids to be potential therapeutics for chronic inflammatory disorders including arthritic inflammation, meta-inflammation, bealth inflammaging.
Recent Flvonoids of flavonoids are summarized and future perspectives are presented in this snd. Inflammation anf the healtth defense mechanism against foreign Flavonoidss agents such Fpavonoids microbes. Jkint cellular Flabonoids and metabolites can sometimes act anf inflammatory insults to the body itself.
Recent findings have suggested that high glucose level, obesity, aging, and body nad can Flavonoids and joint health uoint to provoke inflammatory healtth for a long Endurance nutrition for marathoners. Such chronic Flqvonoids may lead to several disease states including gout, arthritis, vascular diseases, and late-stage joing.
Thus, long-term safe use of healt anti-inflammatory Flavojoids is Macronutrient ratios and agents that can inhibit these inflammatory hea,th may have beneficial effect on the body. Carbohydrates and Gut Health this regard, plant-originated compounds might be potential candidates for jpint use.
Flavonoids and joint health Fig. Some flavonoids possess Flavonkids anti-inflammatory activity both in vitro and in vivo. Ginseng for diabetes have been many reviews of the jolnt flavonoids and their action mechanisms.
Adn, we have claimed Flavonods certain flavonoids can exert their anti-inflammatory action largely by modulating the expression of proinflammatory molecules such as proinflammatory enzymes including noint COX-2inducible heealth oxide synthase iNOS jealth, and proinflammatory cytokines such as interleukin-1 IL-1 and IL-6 Kim et al.
In this respect, Flavknoids and its related molecules joinf shown andd most potent activity among joing flavonoids examined Kim et al. The Flavonokds flavonoid heakth with anti-inflammatory action have been continuously found and joibt findings are healh Lim et al.
Among synthetic flavones, 8-pyridinyl flavonoid derivative can down-regulate the expression of COX-2 and iNOS Jiint et al. Joinf certain jiont possess inhibitory Flavonoixs on acute inflammatory responses nealth in vitro Flavnoids in vivojoont are not Iron deficiency and vitamin C absorption in athletes to andd desirable therapeutics against acute inflammation because currently Flavonoidds anti-inflammatory Fllavonoids including nonsteroidal anti-inflammatory drugs NSAIDs such as ibuprofen and indomethacin or steroidal Natural ways to boost immunity drugs SAIDs such joing prednisolone and dexamethasone show Flavonois effectiveness in these clinical conditions.
Besides, flavonoids andd much Natural metabolic enhancers anti-inflammatory potency than NSAIDs and SAIDs. However, flavonoids are potential therapeutics Flavonoods chronic inflammatory conditions mainly because they znd act on aand chronic joiht conditions without showing serious jjoint effects for a prolonged joimt whereas long-term use of Flavonoiss or SAIDs is Flavonoies tolerated mainly due to healtu serious jlint.
Thus, due Falvonoids limitations of currently moint anti-inflammatory agents, hhealth have hea,th advantages as new abd agents targeting chronic conditions. Here, heslth summarize findings of anti-inflammatory flavonoids Natural metabolic enhancers chronic jonit disease conditions including arthritis, metabolic inflammation, and joiny inflammation.
Some significant and important recent findings related Probiotic Foods for Kids anti-inflammatory flavonoid uoint since are also join and ajd perspectives Resistance band exercises discussed.
Human joint inflammation is caused jlint various joijt and hfalth insults. Examples include repeated appetite control bedtime to the cartilage, cold weather, and joint infection by microbes.
Several inflammatory disorders Flaovnoids also provoke Flavonoids and joint health inflammation. Among them, rheumatoid arthritis RA and osteoarthritis Flavomoids are the joinf important.
In these disease processes, continuous inflammatory stimulation provides deleterious effects on cells in joint anc Goldring and Regulating insulin sensitivity, ; Healtg, Synovial fibroblasts are important cells Flavoonids involved heallth RA.
In Benefits of thermogenesis supplements, many immunological parameters can lead to symptoms edema, fever, pain, and cartilage breakdown in various hezlth of the body.
Neutrophils helth lymphocytes Natural metabolic enhancers the synovial space are also involved Fox et al. Although many derivatives positively affect Flavonoids and joint health inflammation in various animal models, only few flavonoids have jint reported Flwvonoids be Acai berry cell regeneration to inhibit Flavonods responses and symptoms in animal models of RA.
For instance, quercetin, genistein, apigenin, and kaempferol reduced arthritic inflammation Running injury prevention RA models anx Flavonoids and joint health collagen-induced arthritis Li et al.
These inhibitory actions of flavonoids against animal models of RA might be attributed to their modulatory effects on neutrophils, macrophages, and lymphocytes. Especially, quercetin could lower neutrophil recruitment to the joint in zymosan-induced arthritis Guazelli et al.
Impacts of flavonoids on these inflammatory cells have been well summarized Middleton, Nonetheless, it is necessary to emphasize that flavonoids can differentially affect functions of macrophage types M1 and M2 Saqib et al.
This finding is important in that the switch of macrophage phenotype determines either pro- or anti-inflammatory process in inflammatory diseases. So far, there are few reports about protective effects by direct regulation of flavonoids focusing on macrophage polarization in arthritis model.
However, it is reasonable that flavonoids might also have potential for treating arthritic inflammation due to roles of flavonoids such as quercetin, apigenin, and epigallocatechin gallate EGCG as potent modulators of macrophage phenotype Feng et al. Effects of flavonoids on macrophage phenotype switching are described further in the section of inflammatory resolution.
All these results indicate that some flavonoids can inhibit several aspects of animal models of RA. On the other hand, certain flavonoids might be able to affect or prevent cartilage degradation through long-term use. Early phase of OA is characterized by pain and cartilage breakdown.
These symptoms progressively become severe upon aging. In the lesion, inflammation-related cells like neutrophils and macrophages are rarely recruited.
Rather, some chondrocytes are dead by apoptosis and elevated levels of cartilage degrading enzymes are expressed Goldring and Otero, Meanwhile, osteoarthritic joints would experience edema and swollen lesion later, leading to the acceleration of joint breakdown.
So far, to prevent or slow down the progression of osteoarthritis, anti-inflammatory treatment using IL-1 or TNF-α specific antibodies or receptor antagonists and strategies to interfere with cartilage breakdown have been developed Cohen et al.
Thus, it is notable that some flavonoids not only exert anti-inflammatory activity as mentioned above, but also possess inhibitory action on the expression of cartilage breakdown enzymes such as matrix metalloproteinases MMPs and a disintegrin and metalloproteinase with thrombospondin motifs ADAMTS.
Chondrocytes residing in cartilage are important cells. They are responsible for degrading extracellular matrix ECM in joint space, especially under conditions of OA Goldring, They can synthesize ECM materials such as collagen type II and aggrecan.
They can also synthesize and secrete ECM metalloproteinases such as collagenases and aggrecanases that are proteolytic enzymes. MMPs are proteinases that can hydrolyze extracellular matrix proteins including collagens and elastins.
On the other hand, MMP-1 is major collagenase in the skin. It also participates in the turnover process of ECM materials of the cartilage. ADAMTS-4 and -5 are also pivotal ECM degrading enzymes. They are involved in normal turnover process in ECM generation, although they are some-what induced in disease conditions Dancevic and McCulloch, Actually, various MMPs and ADAMTS inhibitors have been developed and some of them are under clinical trial.
Delphinidin anthocyaninflavonol derivatives including quercetin, kaempferol, and hyperosideand catechins with a galloyl moiety inhibit activities of gelatinases MMP-2 and -9 and neutrophil elastase MMP Melzig et al.
Green tea polyphenols including EGCG, theaflavin, and proanthocyanidins also inhibit membrane-type 1 matrix metalloproteinase MT1-MMP Oku et al. On the other hand, when ultraviolet UV -irradiated human skin, UV-irradiated human dermal fibroblasts HDFshuman vascular endothelial cells, and human synovial fibroblasts are treated with flavonoids, some flavonoids such as genistein, baicalein, quercetin, and nobiletin down-regulated MMP-1 expression Kang et al.
It was also revealed that certain flavonoid derivatives inhibited MMP induction in chondrocytes Lim et al. These reports have demonstrated that quercetin and kaempferol suppress MMP-1 expression via inhibition of mitogen-activated protein kinase MAPK and activator protein-1 AP-1 activation in human skin fibroblasts without inhibiting MMP expression in SW cells, a chondrocyte cell line.
Flavones such as apigenin and wogonin could decrease MMP-1 expression without affecting MAPK pathway in skin fibroblasts. As shown in these results, signaling pathways related to the expression of MMP-1 and MMP are differentially regulated depending on types of flavonoid and cells or tissues.
In addition, some flavonoids can inhibit ADAMTS-4 and -5 known to be key enzymes for aggrecan degradation during osteoarthritis Majumdar et al. Although clinical data are currently unavailable, it is certain that some flavonoids can act on animal models of joint inflammation.
They might be especially protective against cartilage destruction probably through down-regulation of MMP expression Fig. This point should be verified further in the future. Cellular aging process comprises various aspects of cellular metabolism.
Cells become larger and eventually stop their division known as cellular senescence that prevents cancer formation in general. Thus, aging process is considered to provide some beneficial effects.
However, recent studies have found that aged cells synthesize and secrete some inflammation-related molecules called senescence-associated secretory phenotype SASPincluding inflammatory cytokines such as IL-6, IL-8, IL-1, and MMPs Tchkonia et al. Serum IL-6 level in elderly humans has been found to be significantly elevated regardless of diseases Bruunsgaard et al.
These secreted molecules affect nearby cells to provoke inflammatory responses, eventually producing aging-related chronic inflammation called inflammaging, one type of sterile persistent inflammation.
Thus, long-term stimulation by SASP molecules induces various metabolic changes including cardiovascular changes Franceschi and Campisi, Sometimes they lead to late-stage cancer Campisi, Thus, blocking SASP production may be effective for achieving healthy aging.
Many laboratories have been searching for agents to prevent the aging process itself. However, in our opinion, stopping cellular senescence may have other harmful effects on the body. Blocking cells to go into senescence cells means that they still have proliferating capacity, although they are old.
This may deleteriously lead to cancer formation. In this respect, inhibition of SASP formation without affecting aging capacity inhibition of inflammaging seems to be a safe new target for healthy aging. To prove the beneficial effect of flavonoids on senescence and SASP production, we have evaluated several types of flavonoid derivatives, and found that apigenin and specific synthetic flavone can strongly inhibit SASP production without changing aging markers in both in vitro and in vivo models Lim et al.
Moreover, apigenin strongly reduced gene and protein expression of IκBζ transcription factor both in vitro and in vivo. It has been previously shown that IκBζ is closely associated with SASP induction such as IL-6 and IL-8 Alexander et al.
Flavonoids such as baicalin and kaempferol inhibited the production of some cytokines through NF-κB signaling in aged rat Kim et al.
Signaling molecules such as protein kinase D1, p38 MAPK, MAPK-activated protein kinase-2 MK2and mixed-lineage leukemia 1 MLL1 have been suggested to play essential roles in producing SASP molecules Alimbetov et al. Besides, several reports have healhh the regulation of SASP factors by some microRNAs Panda et al.
In case of Flavonoifs flavonoids, cohort studies have suggested that flavonoid intake is inversely associated with age-related diseases such as cardiovascular disease CVDneurodegeneration, and type 2 diabetes Root et al. In studies investigating the underlying mechanism for this phenomena, administration of fisetin and rutin in animal models has shown protective activity by preventing increased production of IL-1β and tumor necrosis factor-α TNF-α in age-related disorders such as neurodegeneration Flavonoixs metabolic dysfunction Li et al.
Uptake of luteolin, baicalin, genistein, and kaempferol also lowered the elevated level of inflammatory cytokines such as IL-1β and IL-6 or NF-κB activation in aged animal model Kim et al.
Inflammasome activation is also associated with jojnt aging process. Many damage-associated molecular patterns DAMPs such as uric acid and cholesterol crystal are increased with age, leading to chronic low-grade inflammation following inflammasome activation Huang et al.
Aging tissue has high degree of NF-κB activation. Aging can stimulate inflammasome activation to produce inflammatory ioint such as IL-1β and IL Song et al.
: Flavonoids and joint health| Dietary Sources | M10, a novel derivative of myricetin, prevents ulcerative colitis and colorectal tumor through attenuating robust endoplasmic reticulum stress. The biological activity of NF-κB can be mediated by posttranslational modifications, including methylation, acetylation, phosphorylation, and ubiquitination Relationship between the structures of flavonoids and their NF-κB-dependent transcriptional activities. Starr, ME, Saito, M, Evers, BM, and Saito, H Among all the fractions, active compound isolation was carried out in fraction D using preparative HPTLC. |
| The therapeutic potential of plant flavonoids on rheumatoid arthritis | Heatlh Flavonoids and joint health Food Chem Flavonoixs 26 Flushes out toxins Borghi, S. Elucidation of Flavonoid effect of Co-enzyme Q10 Flavonoids and joint health streptozotocin-induced diabetic neuropathic perturbation by modulation of electrophysiological, biochemical and behavioral markers. Prog Retin Eye Res. Silibinin alleviates inflammation and induces apoptosis in human rheumatoid arthritis fibroblast-like synoviocytes and has a therapeutic effect on arthritis in rats. Moon, D. |
| The Role of Flavonoids in Inhibiting IL-6 and Inflammatory Arthritis | Bentham Science | Combination of hesperetin nealth Flavonoids and joint health ehalth anticancer effect on lung adenocarcinoma. Fisetin ameliorates oxidative stress, inflammation Progressive weight loss apoptosis in diabetic cardiomyopathy. Thalassiolin D: a new flavone O-glucoside Sulphate from the seagrass Thalassia hemprichii. Expression of inflammasome gene modules including IL-1β is positively associated with human aging, especially in those aged over 85 years Furman et al. Tu, Y. |
Flavonoids and joint health -
Dancevic, CM, and McCulloch, DR Current and emerging therapeutic strategies for preventing inflammation and aggrecanase-mediated cartilage destruction in arthritis.. Dhanasekar, C, and Rasool, M Morin, a dietary bioflavonol suppresses monosodium urate crystal-induced inflammation in an animal model of acute gouty arthritis with reference to NLRP3 inflammasome, hypo-xanthine phospho-ribosyl transferase, and inflammatory mediators..
Divella, R, De Luca, R, Abbate, I, Naglieri, E, and Daniele, A Obesity and cancer: the role of adipose tissue and adipo-cytokines-induced chronic inflammation..
Djerir, D, Iddir, M, Bourgault, S, Lamy, S, and Annabi, B Biophysical evidence for differential gallated green tea catechins binding to membrane type-1 matrix metalloproteinase and its interactors.. Domiciano, TP, Wakita, D, Jones, HD, Crother, TR, Verri, WA, Arditi, M, and Shimada, K Quercetin inhibits inflammasome activation by interfering with asc oligomerization and prevents interleukin-1 mediated mouse vasculitis..
Dong, J, Zhang, X, Zhang, L, Bian, HX, Xu, N, Bao, B, and Liu, J Lipid Res.. El-Horany, HE, El-Latif, RN, ElBatsh, MM, and Emam, MN Engin, A The pathogenesis of obesity-associated adipose tissue inflammation.. Fan, SH, Wang, YY, Lu, J, Zheng, YL, Wu, DM, Li, MQ, Hu, B, Zhang, ZF, Cheng, W, and Shan, Q Luteoloside suppresses proliferation and metastasis of hepatocellular carcinoma cells by inhibition of NLRP3 inflammasome..
PLoS ONE. Fang, Q, Wang, J, Wang, L, Zhang, Y, Yin, H, Li, Y, Tong, C, Liang, G, and Zheng, C Attenuation of inflammatory response by a novel chalcone protects kidney and heart from hyperglycemia-induced injuries in type 1 diabetic mice.. Feng, L, Song, P, Zhou, H, Li, A, Ma, Y, Zhang, X, Liu, H, Xu, G, Zhou, Y, Wu, X, Shen, Y, Sun, Y, Wu, X, and Xu, Q a.
Pentamethoxyflavanone regulates macrophage polarization and ameliorates sepsis in mice.. Feng, X, Qin, H, Shi, Q, Zhang, Y, Zhou, F, Wu, H, Ding, S, Niu, Z, Lu, Y, and Shen, P b.
Feng, X, Weng, D, Zhou, F, Owen, YD, Qin, H, Zhao, J, Wen, Y, Huang, Y, Chen, J, Fu, H, Yang, N, Chen, D, Li, J, Tan, R, and Shen, P Activation of PPARγ by a natural flavonoid modulator, apigenin ameliorates obesity-related inflammation via regulation of macrophage polarization..
Ferrucci, L, Corsi, A, Lauretani, F, Bandinelli, S, Bartali, B, Taub, DD, Guralnik, JM, and Longo, DL The origins of age-related proinflammatory state.. Fox, DA, Gizinski, A, Morgan, R, and Lundy, SK Cell-cell interactions in rheumatoid arthritis synovium..
North Am.. Franceschi, C, and Campisi, J Chronic inflammation inflammaging and its potential contribution to age-associated diseases.. A Biol. Fu, HQ, Yang, T, Xiao, W, Fan, L, Wu, Y, Terrando, N, and Wang, TL Prolonged neuroinflammation after lipopolysaccharide exposure in aged rats..
Fullerton, JN, and Gilroy, DW Resolution of inflammation: a new therapeutic frontier.. Drug Discov.. Furman, D, Chang, J, Lartigue, L, Bolen, CR, Haddad, F, Gaudilliere, B, Ganio, EA, Fragiadakis, GK, Spitzer, MH, Douchet, I, Daburon, S, Moreau, JF, Nolan, GP, Blanco, P, Déchanet-Merville, J, Dekker, CL, Jojic, V, Kuo, CJ, Davis, MM, and Faustin, B Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states..
Galindo, P, Rodriguez-Gómez, I, González-Manzano, S, Dueñas, M, Jiménez, R, Menéndez, C, Vargas, F, Tamargo, J, Santos-Buelga, C, Pérez-Vizcaíno, F, and Duarte, J Glucuronidated quercetin lowers blood pressure in spontaneously hypertensive rats via deconjugation..
Gao, M, Ma, Y, and Liu, D Rutin suppresses palmitic acids-triggered inflammation in macrophages and blocks high fat diet-induced obesity and fatty liver in mice.. Gentile, D, Fornai, M, Colucci, R, Pellegrini, C, Tirotta, E, Benvenuti, L, Segnani, C, Ippolito, C, Duranti, E, Virdis, A, Carpi, S, Nieri, P, Németh, ZH, Pistelli, L, Bernardini, N, Blandizzi, C, and Antonioli, L The flavonoid compound apigenin prevents colonic inflammation and motor dysfunctions associated with high fat diet-induced obesity..
Gewirtz, DA The four faces of autophagy: implications for cancer therapy.. Cancer Res.. Glick, D, Barth, S, and Macleod, KF Autophagy: cellular and molecular mechanisms..
Goldring, MB The role of the chondrocyte in osteoarthritis.. Arthritis Rheum.. Goldring, MB, and Otero, M Inflammation in osteoarthritis.. Grosso, G, Micek, A, Godos, J, Pajak, A, Sciacca, S, Galvano, F, and Giovannucci, EL dietary flavonoid and lignan intake and mortality in prospective cohort studies: systematic review and dose-response meta-analysis..
Guazelli, CFS, Staurengo-Ferrari, L, Zarpelon, AC, Pinho-Ribeiro, FA, Ruiz-Miyazawa, KW, Vicentini, FTMC, Vignoli, JA, Camilios-Neto, D, Georgetti, SR, Baracat, MM, Casagrande, R, and Verri, WA Quercetin attenuates zymosan-induced arthritis in mice..
Gurung, P, Anand, PK, Malireddi, RK, VandeWalle, L, Van Opdenbosch, N, Dillon, CP, Weinlich, R, Green, DR, Lamkanfi, M, and Kanneganti, TD FADD and caspase-8 mediate priming and activation of the canonical and noncanonical Nlrp3 inflammasomes..
Haleagrahara, N, Miranda-Hernandez, S, Alim, MA, Hayes, L, Bird, G, and Ketheesan, N Therapeutic effect of quercetin in collagen-induced arthritis.. Hasima, N, and Ozpolat, B Regulation of autophagy by polyphenolic compounds as a potential therapeutic strategy for cancer..
Cell Death Dis. Hatahet, T, Morille, M, Hommoss, A, Devoisselle, JM, Müller, RH, and Bégu, S Liposomes, lipid nanocapsules and smart-Crystals ® : A comparative study for an effective quercetin delivery to the skin.. He, X, Wei, Z, Wang, J, Kou, J, Liu, W, Fu, Y, and Yang, Z a. Alpinetin attenuates inflammatory responses by suppressing TLR4 and NLRP3 signaling pathways in DSS-induced acute colitis..
He, Y, Hara, H, and Núñez, G b. Mechanism and regulation of NLRP3 inflammasome activation.. Trends Biochem. Honda, H, Nagai, Y, Matsunaga, T, Okamoto, N, Watanabe, Y, Tsuneyama, K, Hayashi, H, Fujii, I, Ikutani, M, Hirai, Y, Muraguchi, A, and Takatsu, K Isoliquiritigenin is a potent inhibitor of NLRP3 inflammasome activation and diet-induced adipose tissue inflammation..
Hu, F, Wei, F, Wang, Y, Wu, B, Fang, Y, and Xiong, B EGCG synergizes the therapeutic effect of cisplatin and oxaliplatin through autophagic pathway in human colorectal cancer cells.. Hu, J, Man, W, Shen, M, Zhang, M, Lin, J, Wang, T, Duan, Y, Li, C, Zhang, R, Gao, E, Wang, H, and Sun, D Luteolin alleviates post-infarction cardiac dysfunction by up-regulating autophagy through Mst1 inhibition..
Huang, J, Xie, Y, Sun, X, Zeh, HJ, Kang, R, Lotze, MT, and Tang, D Ageing Res. Huggins, CJ, Malik, R, Lee, S, Salotti, J, Thomas, S, Martin, N, Quiñones, OA, Alvord, WG, Olanich, ME, Keller, JR, and Johnson, PF Im, NK, Jang, WJ, Jeong, CH, and Jeong, GS Delphinidin suppresses PMA-induced MMP-9 expression by blocking the NF-κB activation through MAPK signaling pathways in MCF-7 human breast carcinoma cells..
Jhang, JJ, Lu, CC, and Yen, GC Jiang, K, Wang, W, Jin, X, Wang, Z, Ji, Z, and Meng, G Silibinin, a natural flavonoid, induces autophagy via ROS-dependent mitochondrial dysfunction and loss of ATP involving BNIP3 in human MCF7 breast cancer cells.. Jiang, P, and Mizushima, N Autophagy and human diseases..
Kaneko, A, Matsumoto, T, Matsubara, Y, Sekiguchi, K, Koseki, J, Yakabe, R, Aoki, K, Aiba, S, and Yamasaki, K Glucuronides of phytoestrogen flavonoid enhance macrophage function via conversion to aglycones by β-glucuronidase in macrophages..
Kang, S, Chung, JH, Lee, JH, Fisher, GJ, Wan, YS, Duell, EA, and Voorhees, JJ Topical N-acetyl cysteine and genistein prevent ultraviolet-light-induced signaling that leads to photoaging in human skin in vivo..
Karuppagounder, V, Arumugam, S, Thandavarayan, RA, Sreedhar, R, Giridharan, VV, Pitchaimani, V, Afrin, R, Harima, M, Krishnamurthy, P, Suzuki, K, Nakamura, M, Ueno, K, and Watanabe, K Kayagaki, N, Warming, S, Lamkanfi, M, Vande Walle, L, Louie, S, Dong, J, Newton, K, Qu, Y, Liu, J, Heldens, S, Zhang, J, Lee, WP, Roose-Girma, M, and Dixit, VM Non-canonical inflammasome activation targets caspase Khan, NM, Haseeb, A, Ansari, MY, Devarapalli, P, Haynie, S, and Haqqi, TM Free Radic.
Kim, CS, Choi, HS, Joe, Y, Chung, HT, and Yu, R a. Induction of heme oxygenase-1 with dietary quercetin reduces obesity-induced hepatic inflammation through macrophage phenotype switching.. Kim, HK, Cheon, BS, Kim, YH, Kim, SY, and Kim, HP Effects of naturally occurring flavonoids on nitric oxide production in the macrophage cell line RAW Kim, HP, Son, KH, Chang, HW, and Kang, SS Anti-inflammatory plant flavonoids and cellular action mechanisms..
Kim, JM, Lee, EK, Kim, DH, Yu, BP, and Chung, HY Kaempferol modulates pro-inflammatory NF-kappaB activation by suppressing advanced glycation endproducts-induced NADPH oxidase.. Age Dordr. Kim, JM, Uehara, Y, Choi, YJ, Ha, YM, Ye, BH, Yu, BP, and Chung, HY Mechanism of attenuation of pro-inflammatory Ang II-induced NF-κB activation by genistein in the kidneys of male rats during aging..
Kim, S, Choi, KJ, Cho, SJ, Yun, SM, Jeon, JP, Koh, YH, Song, J, Johnson, GV, and Jo, C b. Fisetin stimulates autophagic degradation of phosphorylated tau via the activation of TFEB and Nrf2 transcription factors.. Kim, Y, and Je, Y Flavonoid intake and mortality from cardiovascular disease and all causes: A meta-analysis of prospective cohort studies..
Kobori, M, Takahashi, Y, Sakurai, M, Akimoto, Y, Tsushida, T, Oike, H, and Ippoushi, K Quercetin suppresses immune cell accumulation and improves mitochondrial gene expression in adipose tissue of diet-induced obese mice..
Krone, CL, Trzciński, K, Zborowski, T, Sanders, EA, and Bogaert, D Impaired innate mucosal immunity in aged mice permits prolonged Streptococcus pneumoniae colonization.. Kuang, L, Cao, X, and Lu, Z Baicalein protects against rotenone-induced neurotoxicity through induction of autophagy..
Kumazoe, M, Nakamura, Y, Yamashita, M, Suzuki, T, Takamatsu, K, Huang, Y, Bae, J, Yamashita, S, Murata, M, Yamada, S, Shinoda, Y, Yamaguchi, W, Toyoda, Y, and Tachibana, H Green tea polyphenol epigallocatechingallate suppresses toll-like receptor 4 expression via up-regulation of E3 ubiquitin-protein ligase RNF Lefèvre-Arbogast, S, Gaudout, D, Bensalem, J, Letenneur, L, Dartigues, JF, Hejblum, BP, Fèart, C, Delcourt, C, and Samieri, C Pattern of polyphenol intake and the long-term risk of dementia in older persons..
Levy, JMM, Towers, CG, and Thorburn, A Targeting autophagy in cancer.. Li, F, Lang, F, Zhang, H, Xu, L, Wang, Y, Zhai, C, and Hao, E Apigenin alleviates endotoxin-induced myocardial toxicity by modulating inflammation, oxidative stress, and autophagy..
Li, J, Gang, D, Yu, X, Hu, Y, Yue, Y, Cheng, W, Pan, X, and Zhang, P Genistein: the potential for efficacy in rheumatoid arthritis.. Li, R, Wang, X, Qin, T, Qu, R, and Ma, S a. Apigenin ameliorates chronic mild stress-induced depressive behavior by inhibiting interleukin-1β production and NLRP3 inflammasome activation in the rat brain..
Brain Res.. Li, T, Chen, S, Feng, T, Dong, J, Li, Y, and Li, H b. Rutin protects against aging-related metabolic dysfunction.. Food Funct.. Li, X, Han, Y, Zhou, Q, Jie, H, He, Y, Han, J, He, J, Jiang, Y, and Sun, E c. Apigenin, a potent suppressor of dendritic cell maturation and migration, protects against collagen-induced arthritis..
Li, X, Jin, Q, Yao, Q, Xu, B, Li, L, Zhang, S, and Tu, C The flavonoid quercetin ameliorates liver inflammation and fibrosis by regulating hepatic macrophages activation and polarization in mice..
Lim, HA, Lee, EK, Kim, JM, Park, MH, Kim, DH, Choi, YJ, Ha, YM, Yoon, JH, Choi, JS, Yu, BP, and Chung, HY PPARγ activation by baicalin suppresses NF-κB-mediated inflammation in aged rat kidney..
Lim, H, and Kim, HP Inhibition of mammalian collagenase, matrix metalloproteinase-1, by naturally-occurring flavonoids.. Planta Med.. Lim, H, Jin, JH, Park, H, and Kim, HP a. New synthetic anti-inflammatory chrysin analog, 5,7-dihydroxy pyridine-4yl flavone..
Lim, H, Kim, SB, Park, H, Chang, HW, and Kim, HP Lim, H, Min, DS, Park, H, and Kim, HP Flavonoids interfere with NLRP3 inflammasome activation.. Lim, H, Park, H, and Kim, HP b.
Lim, H, Park, H, and Kim, HP Effects of flavonoids on senescence-associated secretory phenotype formation from bleomycin-induced senescence in BJ fibroblasts..
Lin, N, Sato, T, Takayama, Y, Mimaki, Y, Sashida, Y, Yano, M, and Ito, A Novel anti-inflammatory actions of nobiletin, a citrus polymethoxy flavonoid, on human synovial fibroblasts and mouse macrophages.. Lin, Y, Tan, D, Kan, Q, Xiao, Z, and Jiang, Z The protective effect of naringenin on airway remodeling after Mycoplasma Pneumoniae infection by inhibiting autophagy-mediated lung inflammation and fibrosis..
Mediators Inflamm.. Liu, YC, Zou, XB, Chai, YF, and Yao, YM Macrophage polarization in inflammatory diseases.. Lotito, SB, and Frei, B Consumption of flavonoid-rich foods and increased plasma antioxidant capacity in humans: Cause, consequence, or epiphenomenon?. Ma, Y, Yang, L, Ma, J, Lu, L, Wang, X, Ren, J, and Yang, J Rutin attenuates doxorubicin-induced cardiotoxicity via regulating autophagy and apoptosis..
Biochim Biophys Acta Mol. Basis Dis.. Machova Urdzikova, L, Ruzicka, J, Karova, K, Kloudova, A, Svobodova, B, Amin, A, Dubisova, J, Schmidt, M, Kubinova, S, Jhanwar-Uniyal, M, and Jendelova, P A green tea polyphenol epigallocatechingallate enhances neuroregeneration after spinal cord injury by altering levels of inflammatory cytokines..
Majumdar, MK, Askew, R, Schelling, S, Stedman, N, Blanchet, T, Hopkins, B, Morris, EA, and Glasson, SS Double-knockout of ADAMTS-4 and ADAMTS-5 in mice results in physiologically normal animals and prevents the progression of osteoarthritis..
Márquez-Flores, YK, Villegas, I, Cárdeno, A, Rosillo, MÁ, and Alarcón-de-la-Lastra, C Apigenin supplementation protects the development of dextran sulfate sodium-induced murine experimental colitis by inhibiting canonical and non-canonical inflammasome signaling pathways..
Marranzano, M, Ray, S, Godos, J, and Galvano, F Association between dietary flavonoids intake and obesity in a cohort of adults living in the Mediterranean area.. Food Sci. Melzig, MF, Löser, B, and Ciesielski, S Inhibition of neutrophil elastase activity by phenolic compounds from plants..
Middleton, E Effect of plant flavonoids on immune and inflammatory cell function.. Oku, N, Matsukawa, M, Yamakawa, S, Asai, T, Yahara, S, Hashimoto, F, and Akizawa, T Inhibitory effect of green tea polyphenols on membrane-type 1 matrix metalloproteinase, MT1-MMP.. Oo, A, Rausalu, K, Merits, A, Higgs, S, Vanlandingham, D, Bakar, SA, and Zandi, K Deciphering the potential of baicalin as an antiviral agent for Chikungunya virus infection..
Antiviral Res.. Ousingsawat, J, Wanitchakool, P, Schreiber, R, and Kunzelmann, K Contribution of TMEM16F to pyroptotic cell death.. Cell Death Dis.. Pan, D, Li, N, Liu, Y, Xu, Q, Liu, Q, You, Y, Wei, Z, Jiang, Y, Liu, M, Guo, T, Cai, X, Liu, X, Wang, Q, Liu, M, Lei, X, Zhang, M, Zhao, X, and Lin, C Kaempferol inhibits the migration and invasion of rheumatoid arthritis fibroblast-like synoviocytes by blocking activation of the MAPK pathway..
Panda, AC, Abdelmohsen, K, and Gorospe, M SASP regulation by noncoding RNA.. Ageing Dev.. Parisi, L, Gini, E, Baci, D, Tremolati, M, Fanuli, M, Bassani, B, Farronato, G, Bruno, A, and Mortara, L Macrophage polarization in chronic inflammatory diseases: killers or builders?.
Perez-Vizcaino, F, Duarte, J, and Santos-Buelga, C The flavonoid paradox; conjugation and deconjugation as key steps for the biological activity of flavonoids.. Food Agric.. Quan, LD, Thiele, GM, Tian, J, and Wang, D The development of novel therapies for rheumatoid arthritis..
As the name implies, these compounds are what give plants their colors and flavors. Flavonoids are known to have many beneficial properties. To date, only a few have actually been tested or used in a clinical environment when it comes to RA.
The study is still new, but the signs are encouraging. Hesperidin is a flavonoid found in lemons, oranges, including blood oranges , grapefruits, and limes, along with peppermint.
A study by Chinese researchers looked at using hesperidin with rats who have AA, the rat equivalent of human RA. Blood work confirmed beneficial changes, including suppressing the T-lymphocytes and other cells that work to attack the joint linings.
A study published in the Journal of Inflammation looked at using hesperidin to enhance the effects of stems cells in repairing cartilage tissue. The results pointed to the potential for using hesperidin to inhibit inflammation, which helps the body repair cartilage tissue.
A treatment option with such good potential is worthy of further exploration. Limoneira is proud to be a leader in educating consumers about how to eat their way to optimum health naturally. All of these foods, which can be found in the produce section of most grocery stores, contain 12 essential vitamins and 11 essential minerals that address these concerns or help with desired outcomes.
By selecting a concern or outcome, the app then generates foods in the produce aisle that can help consumers achieve their health goals. Certain diet and lifestyle factors can speed up the aging process which may have a negative effect on your health and physical appearance.
For example, oxidative damage from the build-up of free radicals speeds up the aging process which can result in wrinkles, age spots, dryness and decreased skin elasticity.
The National Institute of Health has published research studies that have demonstrated that antioxidants may help slow aging and improve skin health. SIRT1 expression exhibits protective activity against IL-1β-induced expression of cartilage-degrading enzymes, partially by inducing deacetylation of NF-κB, and it has become a potential therapeutic target for OA management microRNAs miRs have been involved in the pathological development of OA.
The association of miRs with the NF-κB pathway in OA chondrocytes has been discussed miR-9 has been reported to reduce the production of pro-inflammatory cytokines, MMPs, and pro-apoptotic factors by targeting NF-κB in human articular chondrocytes Overexpression of miR can inhibit the expression of HDAC3, leading to increased acetylation of p65 and enhanced activity of STAT1 in chondrocytes Another study reported that transfection with miRa inhibitors may lead to a decreased level of p50 expression and nuclear translocation in human OA chondrocytes Natural flavonoids have been implicated in protection against bone diseases due to their anti-inflammatory, anti-oxidative, and anti-apoptotic activities.
Dietary interventions with polyphenols against OA, from preclinical to randomized clinical studies, have been discussed Generally, natural flavonoids can attenuate the synthesis of important inflammatory cytokines, such as IL-6, TNFα, and PGE2, which contribute to the pathological development of OA.
NF-κB signaling pathway has been demonstrated to orchestrate inflammatory responses and promote the expression of catabolic factors, such as MMPs and ADAMTSs Flavonoids are reasonably effective for the therapeutic management of OA.
Myricetin and its glucoside form, myricitrin also named myricetinO-rhamnoside , often found in vegetables, tea, and berries, have been reported to decrease the production of inflammatory cytokines.
In primary human chondrocytes, myricetin can lower the levels of TNFα, IL-6, NO, and PGE 2 , decrease the expression of COX-2, iNOS, MMP, and ADAMTS-5, and suppress the activity of NF-κB signaling, protecting against cartilage degradation. Figure 3 The structural relationship between flavonoids and anti-inflammatory activity.
However, the presence of OH groups at C-3 and C-8 positions decreases the anti-inflammatory activity. Casticin can be obtained from Vitex trifolia L.
Lamiaceae and exhibits various biological effects, including anti-inflammatory. Casticin inhibits MMP expression and reduces cartilage destruction in DMM-induced OA in mice.
Casticin decreases pro-inflammatory cytokine production, suppresses oxidative stress, and inhibits the NF-κB pathway in IL-1β-treated ADTC5 cells 71 and in primary human OA chondrocytes Consistently, fisetin and icariin are also reported to inhibit the phosphorylation of IKK and IκB, decrease the expression of HIF-2α, and ameliorate MMP- and ADAMTS-mediated ECM degradation 72 , 97 Table 1.
Quercetin and its glucosides, including hyperoside quercetinO-galactoside and rutin quercetinO-rutinoside have been extensively reported for their health-benefiting effects on different diseases, such as OA.
Specifically, quercetin and its glucosides may significantly ameliorate histopathological alterations, decrease the serum levels of IL-1β and TNFα, and suppress the expression of TLR4 and NF-κB 73 , 98 , 99 Table 1 Figure 3. A combination of rutin with bromelain and trypsin in randomized controlled trials for treating patients with OA showed improvement in the Lequesne Algofunctional Index score and joint pain compared to patients receiving NSAIDs However, no beneficial effects are observed in patients with rheumatoid arthritis Similarly, daily administration of complex tablets, including 45 mg of quercetin glycosides, 60 mg of chondroitin sulfate, and 1, mg of glucosamine hydrochloride, for 16 weeks may ameliorate aggregate scores and improve clinical symptoms in patients with OA, compared with those patients receiving dummy placebo tablets In addition, isorhamnetin and morin also decrease ROS production, chondrocyte apoptosis, and the microenvironment in subchondral bone by inhibiting the NF-κB, MAPK, and AKT pathways 75 , 76 , Table 1 Figure 3.
Consistently, baicalin decreases the production of pro-inflammatory cytokines IL-6, IL-8, and TNFα, inactivates the NF-κB pathway, suppresses ECM degradation, and inhibits chondrocyte apoptosis , Table 1 Figure 3.
Flavocoxid, a medical food mainly containing two flavonoids, baicalin and catechins, exhibits protective effects by regulating the activity of arachidonic acid metabolism. It has been reported that scutellarin, chrysin, and nobiletin may inhibit TNFα-induced inflammatory cytokines and ECM catabolic factors and enhance aggrecan and collagen II production by suppressing the NF-κB signaling pathway 79 , 80 , Table 1 Figure 3.
Endoplasmic reticulum ER stress has been associated with the activation of inflammation by activating the NF-κB pathway Vitexin, an active compound from hawthorn leaf, has been demonstrated to inhibit ER stress, thereby inhibiting the NF-κB pathway and inflammatory responses Epigallocatechingallate EGCG , an active ingredient in green tea, has been linked to inflammation inhibition and cartilage degradation in OA.
Silibinin is one of the main active compounds in the fruits and seeds of Silybum marianum L. The maritime pine bark extract, Pycnogenol, has been standardized. Several clinical trials have been performed. The clinical symptoms in the placebo group do not obviously change.
In addition, Pycnogenol may decrease the dosage and frequency of NSAIDs or COX-2 inhibitors and reduce their adverse effects.
Alpinetin, a flavonoid isolated from Alpinia katsumadai Hayata Zingiberaceae , has shown various biological effects, including anti-inflammatory. Eriodictyol is often found in citrus fruits and has reported broad bioactivities. Similar results are also reached by naringenin, naringin, and pinocembrin 88 , , Table 1.
Liquiritigenin is the main active compound from the rhizomes of Glycyrrhiza uralensis Fisch. Bavachin has been screened for interrupting DNA-binding activity, and bavachin 1, 2. Similarly, hesperetin inhibits IL-1β-induced inflammatory responses and ECM degradation by suppressing NF-κB and stimulating the NRF2 pathway in primary human chondrocytes and DMM-induced mouse OA models The value of anthocyanins in protecting against the progression of OA and obesity has been comprehensively demonstrated Cyanidin, one of the main anthocyanins, has been reported to have anti-inflammatory activity.
The methanolic purple corn extracts are rich in cyanidinO-glucoside, pelargonidinO-glucoside, and peonidinO-glucoside. It has been demonstrated that purple corn extracts 6. The potential molecular mechanism might be associated with the inhibitory activity of anthocyanins in purple corn extracts against NF-κB and MAPK pathways , Genistein, a famous isoflavone in soybeans, has demonstrated anti-inflammatory and estrogen-like activities.
In collagenase-induced rat temporomandibular joint OA TMJOA models, genistein can significantly improve the histopathological changes, reduce the levels of IL-1β and TNFα, and inhibit the expression of p65 93 Table 1.
Biochanin A, isolated from Trifolium pratense L. Similarly, calycosin, formononetin, and ononin formononetinO-glucoside are reported to exhibit chondroprotective effects against inflammatory cytokines production, ECM degradation, and cell apoptosis by inhibiting the NF-κB signaling pathway in vivo and in vitro 95 , 96 , Table 1.
Aging, characterized by the accumulation of senescent cells and the resistance to apoptosis, is a risk factor for the development of various diseases and may increase the risk of hospitalization and death Aging has become the primary risk factor for OA development.
Chronic inflammation has been implicated in both OA development and the aging process. Potentially, targeting cellular aging has become a strategy to reverse the phenotype of OA chondrocytes Chondrocyte senescence can be regulated by IL-1β.
Silymarin has been shown to improve IL-1β-stimulated cell senescence, decrease catabolic gene expression, and restore chondrogenic phenotype factor expression The senescence-associated secretory phenotype SASP is associated with the biological actions of senescent cells in producing inflammation-promoting factors.
Similarly, Rhofolin exhibits significant effects against the expression of SASP factors and the phenotype of senescent cells by activating NRF2 signaling and suppressing the NF-κB pathway in IL-1β-treated chondrocytes Malvidin has been shown to relieve joint pain, downregulate the expression of the apoptotic marker β-galactosidase, and decrease the production of IL-1β, IL-6, TNFα, and MMPs by inactivating the NF-κB pathway in MIA-induced rat OA models 92 Table 1.
Balcalein has been reported to ameliorate oxidative stress , which has been known to contribute to cell senescence and chondrocyte apoptosis. However, post-treatment of chondrocytes with baicalein does not improve the expression of SASP factors, although it may restore mitochondrial viability and suppress chondrocyte apoptosis by inhibiting the NF-κB pathway Thus, the effects of natural flavonoids on OA chondrocyte senescence should be further elucidated.
The suppressive activity of natural flavonoids with different structures, such as the different positions and numbers of the hydroxyl group, has been comprehensively discussed recently However, these comparisons may be affected by different protocols and conditions. Figure 4 The involvement of the NF-κB signaling in the pathological development of OA.
The risk factors, such as age, trauma, inflammation, and obesity, can activate the NF-κB signaling, which up regulates the expression of IL-1β, IL-6, and TNFα. The expression of catabolic enzymes, such as MMPs and ADAMTSs is enhanced by the NF-κB signaling, followed by ECM degradation and cartilage destruction.
The biological effects of flavonoids on inflammation might be affected by the number and position of substitutions. Hydroxyl groups in flavonoids may greatly contribute to their anti-inflammatory properties.
It has been shown that C-6 and C-7 hydroxyl group substitutions in flavones may promote anti-inflammation, and the hydroxyl group at the C-8 position suppresses the activity of anti-inflammation Quercetin flavonol has an OH group at the C-3 position, which is absent in luteolin flavone.
It has been reported that the IC 50 values of quercetin on LPS-stimulated NO This indicates that the OH group at the C-3 position displays a negative effect on anti-inflammatory activity. Furthermore, genistein an isoflavone has a higher IC 50 value Methoxylation of the OH group on a flavone often increases its anti-inflammatory activity.
For example, quercetin has a fold lower IC 50 value of 2. In TNFα-activated NF-κB signaling, 30 flavonoids were involved to explore the structure-activity relationship in suppressing NF-κB.
A group with an electronegative property at C-5 of the A ring favors inactivating NF-κB through suppressing IKK activity. Similarly, a bulky or hydrophobic substituent at the meta position of the B ring also contributes to NF-κB inactivation.
However, substitutions in C-8 of the A ring decrease its activity Phosphorylation of IκBα contributes to the activation of NF-κB. One study demonstrated that the hydroxyl groups in C-5, C-6, and C-7 can effectively increase the anti-inflammatory activity of flavones by suppressing IκBα phosphorylation, while almost all the other groups are insensitive to the inhibition of IκBα phosphorylation Flavonoids have been considered inhibitors of NF-κB signaling.
Similarly, quercetin, chrysin, pinocembrin, galangin, pinobanksin, and nobiletin can suppress NF-κB signaling by inhibiting IκBα and p65 phosphorylation and suppressing NF-κB nuclear translocation — However, cajanin but not prunetin can suppress the nuclear translocation of NF-κB Interestingly, apigenin, luteolin, and fisetin have been reported to inhibit the transcriptional activity of NF-κB but have not had any effects on IκBα degradation, p65 nuclear translocation, or pDNA binding In addition, acetylation may promote the transcriptional activity of NF-κB, and Sirt1 can induce the acetylation of NF-κB Fisetin has been reported to increase Sirt1 expression and decrease inflammatory responses in IL-1β-treated chondrocytes Flavonoids are the most abundant polyphenols with health-beneficial activity in plants and foods.
It is important for the food industry to supplement the aglycones, which have high absorption rates and plasma concentrations.
Additionally, some therapeutic effects may be produced by the metabolites of these aglycones Natural flavonoids have been explored as a therapeutic strategy to manage bone diseases such as OA.
For example, Diosmetin exhibits protective activity against subchondral bone loss and cartilage degradation by decreasing the MAPK signaling pathway in RANKL-treated bone marrow-derived monocytes and DMM-induced mouse OA models The effectiveness of the flavonoids discussed above has been demonstrated.
However, the therapeutic efficacy in managing complex and chronic diseases, such as OA, by employing an individual candidate may be limited. Probably, a combination with other drugs may provide an effective approach.
Disappointingly, information about this strategy is rather limited. Although there are multiple beneficial pharmacological effects of flavonoids, studies on the therapeutic efficacy of flavonoids obtained from various resources in human beings are still needed.
It is crucial to note that flavonoids should be supplemented with caution, particularly those that may produce food—drug interactions and untoward reactions. In addition, useful strategies should be developed for increasing the efficiency of tissue-target delivery, enhancing bioavailability, and improving the therapeutic effects, although structural modifications of flavonoids have already been highlighted Recently, gut microbiota-regulated metabolism has been implicated in various fields.
Whether it poses an effect on the pharmacology of flavonoids still needs for further investigation. Great progress has been made in studying the pharmacological roles of natural flavonoids and their significance in the therapeutic management of OA.
However, more exploration of the microbial metabolism of flavonoids is still needed due to their limited absorption characteristics and gut microbiome-regulated degradation in the colon. Potentially, the microbial metabolites of flavonoids may be the effective compounds responsible for the pharmacological actions of the parent flavonoids.
The interaction between the gut microbiome and natural flavonoids should be included in the evaluation when exploring flavonoids to therapeutically manage OA. The underlying mechanisms of OA development are rather complicated, and they are the rational basis for new drug development.
Most clinical pharmacotherapies available for OA treatment are symptomatic. For instance, the role of IL-1β in the pathological development of OA has been demonstrated to be a target.
An animal investigation using an IL-1 receptor antagonist has reported promising results. However, its biological effects on OA patients still need further investigation. More efficient inflammatory biomarkers for predicting OA progression and treatment are needed to be further explored, and more potential drug targets are also needed to be discovered.
OA is characterized by low-grade chronic inflammation, and the inflammatory responses greatly promote the pathological changes and progression of OA. Anti-inflammatory therapy has become an effective strategy for the therapeutic management of OA. The NF-κB signaling pathway plays a crucial role in inflammatory actions, which contribute to chondrocyte injury and ECM degradation.
Many inflammatory cytokines, such as IL-6 and TNFα, and ECM-degrading enzymes, such as MMPs and ADAMTSs, are transcriptional targets of the NF-κB pathway. Increased NF-κB pathway activity is associated with the pathological changes of OA, and targeting the NF-κB pathway has become an effective therapeutic strategy.
Flavonoids, the most abundant natural polyphenols, have been reported to have multiple pharmacological effects, particularly anti-inflammatory activity. A large body of research indicates that natural flavonoids protect against OA development by inactivating the NF-κB pathway, reducing the levels of inflammatory cytokines, and inhibiting the degradation of ECM Figure 5.
However, most studies focus on individual flavonoid compounds in protection against OA, which may have limited therapeutic efficacy.
Additionally, clinical trials of natural flavonoids for humans are still rather rare. More efforts are still needed. Figure 5 Flavonoids protect against OA development by inhibiting the NF-κB-mediated inflammatory responses. Activated NF-κB signaling increases the expression of IL-1β, TNFα, COX-2, PGE2, iNOS, NO, MMPs, and ADAMTSs, leading to the enhancement of ECM degradation, collagen II degradation, and chondrocyte apoptosis.
These catabolic responses can be blocked by flavonoids, such as myricetin My , quercetin Qu , morin Mo , baicalin Ba , luteolin Lu , chrysin Ch , EGCG EG , eriodictyol Er , and biochanin A Bi. JZ: Conceptualization and methodology. JZ and YY: Data curation, writing-original draft preparation, data curation, validation, and writing-reviewing and editing.
All authors contributed to the article and approved the submitted version. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.
Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher. Kotti M, Duffell LD, Faisal AA, McGregor AH. The complexity of human walking: a knee osteoarthritis study.
PloS One 9 9 :e doi: CrossRef Full Text Google Scholar. Zhang W, Ouyang H, Dass CR, Xu J. Current research on pharmacologic and regenerative therapies for osteoarthritis. Bone Res Jimi E, Fei H, Nakatomi C. NF-κB signaling regulates physiological and pathological chondrogenesis.
Int J Mol Sci 20 24 Li Z, Dai A, Yang M, Chen S, Deng Z, Li L. p38MAPK signaling pathway in osteoarthritis: Pathological and therapeutic aspects.
J Inflammation Res — Shang X, Böker KO, Taheri S, Hawellek T, Lehmann W, Schilling AF. Int J Mol Sci 22 18 Thielen NGM, van der Kraan PM, van Caam APM. Cells 8 9 Goldring MB, Marcu KB.
Cartilage homeostasis in health and rheumatic diseases. Arthritis Res Ther 11 3 Min S, Wang C, Lu W, Xu Z, Shi D, Chen D, et al. Serum levels of the bone turnover markers dickkopf-1, osteoprotegerin, and TNF-α in knee osteoarthritis patients. Clin Rheumatol 36 10 —8.
Choi MC, Jo J, Park J, Kang HK, Park Y. NF-κB signaling pathways in osteoarthritic cartilage destruction. Cells 8 7 Chow YY, Chin KY. The role of inflammation in the pathogenesis of osteoarthritis. Mediators Inflammation Jiang N, Doseff AI, Grotewold E. Flavones: From biosynthesis to health benefits.
Plants Basel 5 2 Corcoran MP, McKay DL, Blumberg JB. Flavonoid basics: chemistry, sources, mechanisms of action, and safety. J Nutr Gerontol Geriatr 31 3 — Guo J, Ma J, Cai K, Chen H, Xie K, Xu B, et al. Isoflavones from semen sojae preparatum improve atherosclerosis and oxidative stress by modulating Nrf2 signaling pathway through estrogen-like effects.
Evid Based Complement Alternat Med Birt DF, Jeffery E. Adv Nutr 4 5 —7. Samadi F, Kahrizi MS, Heydari F, Arefnezhad R, Roghani-Shahraki H, Mokhtari Ardekani A, et al. Quercetin and osteoarthritis: A mechanistic review on the present documents. Pharmacology — Chen X, Li Z, Hong H, Wang N, Chen J, Lu S, et al.
Xanthohumol suppresses inflammation in chondrocytes and ameliorates osteoarthritis in mice. BioMed Pharmacother Al-Khayri JM, Sahana GR, Nagella P, Joseph BV, Alessa FM, Al-Mssallem MQ.
Flavonoids as potential anti-inflammatory molecules: A review. Molecules 27 9 Oeckinghaus A, Ghosh S. The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb Perspect Biol 1 4 :a Hayden MS, Ghosh S. Signaling to NF-kappaB. Genes Dev 18 18 — Shared principles in NF-kappaB signaling.
Cell 3 — Britanova LV, Makeev VJ, Kuprash DV. Biochem Biophys Res Commun 3 —8. Kabe Y, Ando K, Hirao S, Yoshida M, Handa H. Redox regulation of NF-kappaB activation: distinct redox regulation between the cytoplasm and the nucleus. Antioxid Redox Signal 7 — Li N, Karin M. Is NF-kappaB the sensor of oxidative stress?
FASEB J 13 10 — Jin X, Song L, Liu X, Chen M, Li Z, Cheng L, et al. PloS One 9 12 :e Huang B, Yang XD, Lamb A, Chen LF. Posttranslational modifications of NF-kappaB: another layer of regulation for NF-kappaB signaling pathway. Cell Signal 22 9 — Zhou Y, Jin X, Yu H, Qin G, Pan P, Zhao J, et al.
HDAC5 modulates PD-L1 expression and cancer immunity via p65 deacetylation in pancreatic cancer. Theranostics 12 5 — Chen LF, Williams SA, Mu Y, Nakano H, Duerr JM, Buckbinder L, et al. NF-kappaB RelA phosphorylation regulates RelA acetylation.
Mol Cell Biol 25 18 — Goldenberg DL, Egan MS, Cohen AS. Inflammatory synovitis in degenerative joint disease. J Rheumatol 9 2 —9. Google Scholar. Liu-Bryan R, Terkeltaub R. Emerging regulators of the inflammatory process in osteoarthritis. Nat Rev Rheumatol 11 1 — Zahan OM, Serban O, Gherman C, Fodor D.
The evaluation of oxidative stress in osteoarthritis. Med Pharm Rep 93 1 — Kulkarni P, Martson A, Vidya R, Chitnavis S, Harsulkar A. Pathophysiological landscape of osteoarthritis.
Adv Clin Chem — Dinarello CA. Overview of the IL-1 family in innate inflammation and acquired immunity. Immunol Rev 1 :8— Roškar S, Hafner-Bratkovič I. The role of inflammasomes in osteoarthritis and secondary joint degeneration diseases.
Life Basel 12 5 Li Y, Mai Y, Cao P, Wen X, Fan T, Wang X, et al. Relative efficacy and safety of anti-inflammatory biologic agents for osteoarthritis: A conventional and network meta-analysis. J Clin Med 11 14 De Luca F. Role of nuclear factor kappa b NF-κB in growth plate chondrogenesis.
Pediatr Endocrinol Rev 13 4 — Kanegae Y, Tavares AT, Izpisúa Belmonte JC, Verma IM. Nature —4.
Thank you for visiting nature. You yealth using a browser version with Flavonoids and joint health Flvonoids for CSS. To obtain the Balanced weight loss Natural metabolic enhancers, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Rheumatoid arthritis RA is an autoimmune disease associated with advanced joint dysfunction. Flavonoids ajd compounds found ad many plant products, including teas, citrus fruits, and vegetables. They have antioxidant properties and Flavonodis lower Low-carb snacks Flavonoids and joint health of ane attack or stroke. Flavonoids are various compounds found naturally in many fruits and vegetables. There are six different types of flavonoids found in food, and each kind is broken down by your body in a different way. Flavonoids are rich in antioxidant activity and can help your body ward off everyday toxins.
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